[go: up one dir, main page]

WO2012030231A1 - Composition antifongique - Google Patents

Composition antifongique Download PDF

Info

Publication number
WO2012030231A1
WO2012030231A1 PCT/NZ2011/000172 NZ2011000172W WO2012030231A1 WO 2012030231 A1 WO2012030231 A1 WO 2012030231A1 NZ 2011000172 W NZ2011000172 W NZ 2011000172W WO 2012030231 A1 WO2012030231 A1 WO 2012030231A1
Authority
WO
WIPO (PCT)
Prior art keywords
honey
composition
lactoferrin
yeast
growth
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/NZ2011/000172
Other languages
English (en)
Inventor
Swapna Gannabathula
Jonathan Mcdonald Counsell Stephens
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Comvita New Zealand Ltd
Original Assignee
Comvita New Zealand Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Comvita New Zealand Ltd filed Critical Comvita New Zealand Ltd
Priority to EP11822182.9A priority Critical patent/EP2611453B1/fr
Priority to CA2809535A priority patent/CA2809535C/fr
Priority to AU2011296641A priority patent/AU2011296641B2/en
Priority to US13/819,629 priority patent/US20130273020A1/en
Publication of WO2012030231A1 publication Critical patent/WO2012030231A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/482—Serine endopeptidases (3.4.21)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/64—Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/63—Arthropods
    • A61K35/64—Insects, e.g. bees, wasps or fleas
    • A61K35/644—Beeswax; Propolis; Royal jelly; Honey
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/40—Transferrins, e.g. lactoferrins, ovotransferrins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/44—Oxidoreductases (1)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • the application relates to an antifungal composition. More specifically, the application relates to a composition for use in inhibiting yeast growth including a combination of lactoferrin and either honey, a honey extract or a honey analogue.
  • Honey is well known and discussed in the art for its antimicrobial effects. Honey inhibits microbial growth due to a variety of factors, all of which overwhelm the microbe defence mechanisms. Examples of anti-microbial factors include the smolarity of honey (and resulting low water activity), the low pH of honey, the presence of hydrogen peroxide, the presence of bee defensins and other compounds such as methylglyoxal (MGO) and phenolic compounds. Fungal treatments using honey are less widely documented although it is known that honey has antifungal properties. Metal chelators including lactoferrin are well known in the art. Chelators are essentially molecules that react quickly with free hydrogen or metal ions binding up the ions within the molecule and removing them from a solution.
  • chelators can have very important physiological effects. In particular, they help the body regulate the presence of trace metals in the body, both preventing an overdose as well as providing a reservoir of metal ions for use when trace metals become low.
  • Haemoglobin is one important metal (iron) chelator in the body that ensures stocks of iron remain present as it is an essential element in normal metabolism.
  • Metal ions in general are important cofactors to many biological reactions and an overabundance of chelating compounds essentially starves the normal metabolic process.
  • Metals that may be chelated include the transition metals including calcium, magnesium, iron, copper and zinc.
  • Known metal chelators are varied and include (but are not limited to) lactoferrin, shellfish extracts (including those from green lipped mussel and oysters) particularly those containing cavortin protein, nut tannins, seaweeds, green tea, phytic acid, potato peel and many others.
  • Existing metal chelators are known to deprive microbes of essential minerals required for growth.
  • iron is a necessary trace mineral for haemoglobin enzyme activity.
  • the application broadly relates to the combination of honey, an active fraction of honey or a honey analogue with lactoferrin as a means to inhibit the growth of yeasts.
  • a yeast inhibitive composition including: a. a therapeutically effective amount of at least one active honey; and
  • a yeast inhibitive composition including: a. a therapeutically effective amount of at least one bioactive fraction of active honey wherein the monosaccharides of the honey have been removed; and b. a therapeutically effective amount of lactoferrin.
  • a yeast inhibitive composition including: a. a therapeutically effective amount of at least one honey analogue containing
  • monosaccharides water and either or both of DHA and MGO and having at least one further characteristic being: a pH of 3.0 to 5.0; phenolics characteristic of active honeys; bee defensins, a water activity less than 0.7; and b. a therapeutically effective amount of lactoferrin.
  • a method of inhibiting yeast growth by administrating a composition substantially as described above to a subject in need thereof.
  • a composition substantially as described above in the manufacture of a medicament to inhibit yeast growth.
  • a yeast inhibitive wound dressing including a composition substantially as described above.
  • a yeast inhibitive aqueous based medicament including a composition substantially as described above.
  • the inventor's have unexpectedly found that the combination of honey, a honey fraction or a honey analogue along with lactoferrin has a synergistic effect on inhibiting yeast growth. This inhibition effect is far greater than the individual components themselves. This synergism is not predictable from the art and appears to relate to an interaction between compounds or characteristics of honey and lactoferrin. The inhibition effect appears to be highly synergistic. For example, only very dilute quantities of honey and lactoferrin are required to achieve inhibition and the inhibition effect goes beyond what either of the components achieve alone.
  • Figure 1 shows a graph illustrating Candida albicans growth when subjected to
  • Figure 2 shows a graph illustrating Candida albicans growth when subjected to
  • Figure 3 shows a graph illustrating Candida albicans growth when subjected to
  • the application broadly relates to the combination of honey, an active fraction of honey or a honey analogue with lactoferrin as a means to inhibit the growth of yeasts.
  • 'honey' refers to naturally produced honey (i.e. produced by bees) containing at least a mix of glucose, fructose, water and glucose oxidase enzyme.
  • the term 'honey analogue' refers to a mixture of 30-50% glucose, 30-50% fructose, 1 -18% water and either or both of glucose oxidase enzyme and/or hydrogen peroxide. Where the analogue is used shortly after production, hydrogen peroxide itself may be used. Where the analogue may be stored for a period of time, the analogue by preference contains glucose oxidase enzyme. As may be appreciated, glucose oxidase enzyme converts sugars into hydrogen peroxide that also results in a lower pH. If hydrogen peroxide alone is used and then the analogue stored, it is possible that the peroxide level will decrease by a normal reduction equilibrium and the pH level then increase. Using glucose oxidase enzyme ensures a steady level of hydrogen peroxide and hence steady pH. The quantities used are intended to approximate the composition of naturally produced honey.
  • honey fractions referred to in this specification include a UMF or non-peroxide activity containing portion of the honey as well as other non-saccharide components including compounds selected from: phenolics, bee defensins, and catalase enzyme.
  • 'chelator' and grammatical variations thereof refer to compounds or substances containing compounds that act to scavenge and bind metal ions in a solution.
  • 'active honey' refers to a honey with an antimicrobial activity in the absence of.
  • hydrogen peroxide referred to interchangeably as a honey containing UMF activity, MGO activity or containing DHA compound.
  • the term 'Unique Manuka Factor', 'UMF' and 'non-peroxide activity' refer to the activity of honey not directly attributable to the antimicrobial effects of honey conferred from the normal honey pH and osmolarity, for example that observed and measured in a naturally derived clover honey.
  • the term 'U F' may be used interchangeably with methylglyoxal ( GO) concentration or dihydroxyacetone (DHA) concentration since MGO is known to be the compound attributable to UMF activity and DHA is a precursor compound of MGO also present in UMF honey and attributable to the UMF activity.
  • the term 'gelling agent' or grammatical variations thereof refers to an agent that, in the absence of liquid is not a gel, but the agent is able to form a gel in the presence of liquid.
  • dressing' refers to any covering that may be applied to a lesion where lesions encompass infected and non-infected abrasions, cuts, bits, burns, wounds, ulcers, abscesses, surgical wounds, fungating tumours and pressure sores.
  • bioactive' refers to the composition containing biologically active compounds that inhibit yeast growth.
  • the term 'therapeutically effective' with reference to an amount or dosage of a composition or medicament noted refers to an amount of a composition that is sufficient to effectively inhibit yeast growth.
  • the term 'about' refers to a quantity, level, value, number, frequency, percentage, dimension, size, weight, or length that varies by as much as 30, 25, 20,15, 10,9, 8, 7, 6, 5, 4, 3, 2 or 1 % to a reference quantity, level, value, number, frequency, percentage, dimension, size, weight, or length.
  • a yeast inhibitive composition including: a. a therapeutically effective amount of at least one active honey; and b. a therapeutically effective amount of lactoferrin.
  • a yeast inhibitive composition including: a. a therapeutically effective amount of at least one bioactive fraction of active honey wherein the monosaccharides of the honey have been removed; and b. a therapeutically effective amount of lactoferrin.
  • a yeast inhibitive composition including: a. a therapeutically effective amount of at least one honey analogue containing monosaccharides, water and either or both of DHA and MGO and having at least one further characteristic being: a pH of 3.0 to 5.0; phenolics characteristic of active honeys; bee defensins, a water activity less than 0.7; and b. a therapeutically effective amount of lactoferrin.
  • the inventor's have unexpectedly found that the combination of honey, a honey fraction or a honey analogue along with lactoferrin has a synergistic effect on inhibiting yeast growth. This inhibition effect is far greater than the individual components themselves. This synergism is not predictable from the art and appears to relate to an interaction between compounds or characteristics of the honey and lactoferrin. The inhibition effect appears to be highly synergistic. For example, only very dilute quantities of honey and lactoferrin are required to achieve inhibition and the inhibition effect goes beyond what either of the components achieve alone.
  • Microbial growth may be inhibited by at least about 20% over a 24-hour time period as measured via optical density. Microbial growth may be inhibited by at least about 40% over a 24-hour time period as measured via optical density. Microbial growth may be inhibited by at least about 60% over a 24-hour time period as measured via optical density. Microbial growth may be inhibited by at least about 80% over a 24-hour time period as measured via optical density. Microbial growth may be inhibited by 100% over a 24-hour time period as measured via optical density.
  • the yeast may be from the genus Candida.
  • the yeast may be a strain of Candida albicans. While many Candida species are comparatively benign, some Candida may be harmful and some that are normally benign may become problematic if the host immune system is comprised or if the Candida infects the wrong location.
  • Candida albicans in particular may be problematic and is associated with candidiasis or thrush in humans and other animals especially in immune- compromised patients.
  • Literature suggests that systemic infections of the bloodstream and major organs with Candida yeasts particularly in immune-comprised patients affect over 90,000 people a year in the USA with a 40-50% mortality. Candida infection is therefore a key issue.
  • Candida can cause superficial infections such as oropharyngeal candidiasis (thrush) and vulvovaginal candidiasis (vaginal Candidiasis). Oral candidiasis is common in elderly denture wearers.
  • Candida infections can be cured with topical or systemic antifungal medications (commonly over-the-counter treatments like miconazole or clotrimazole).
  • Miconazole may have unwanted side effects from drug interactions as it may be absorbed into the intestinal tract when used orally.
  • Clotrimazole may also have drug interactions and a range of other side effects including skin rash, hives, blistering, burning, itching, peeling, redness, stinging, swelling, or other sign of skin irritation. Use of these over the counter treatments can therefore be problematic.
  • candidiasis may become a systemic disease producing abscess,
  • thrombophlebitis thrombophlebitis, endocarditis, or infections of the eyes or other organs.
  • composition described using honey and lactoferrin uses two natural based products that are relatively benign and have minimal if any side effects offering a significant advantage over art treatments.
  • honey used to treat Candida is somewhat counter intuitive as Candida ferment glucose and other sugars to acid and gas, sucrose to acid. Since sugars are key components in honey, use of honey would be expected to encourage Candida growth as opposed to inhibit growth.
  • the honey used or honey from which the honey fraction is derived from may have both peroxide and non-peroxide activity i.e. it is an 'active' honey.
  • Peroxide activity stems from the activity of the enzyme glucose peroxidase present in all honeys.
  • the enzyme originates from bees and catalyses the production of hydrogen peroxide upon dilution of the honey, for example when placed on a wound.
  • Non-peroxide activity is often used interchangeably with the measurement of 'unique manuka factor' or 'UMF' activity and more recently MGO concentration and refers to the honey retaining its antimicrobial activity in the absence of the production of hydrogen peroxide.
  • the honey used may have the compounds dihydroxyacetone (DHA), methylglyoxal (MGO) or both present.
  • DHA dihydroxyacetone
  • MGO methylglyoxal
  • Recent research has found the presence of DHA and MGO in 'active' honeys such as manuka honey.
  • DHA appears to be a precursor for MGO and MGO appears to contribute to the anti-microbial effects of active honeys.
  • Honey has inherent physical characteristics such as low pH and osmolarity that deter microbial growth. However, honeys with non-peroxide activity are often desired or preferred in medical applications. This is because of their enhanced anti-microbial effects and as a result may be termed 'active' honeys.
  • Suitable honeys include those substantially derived from plants of the Leptospermum species.
  • the term 'Leptospermum species' refers to a genus of plants in the myrtle family Myrtaceae and includes: Leptospermum scoparium, Leptospermum polygalifolium, Leptospermum
  • the phrase 'substantially derived from a Leptospermum sp.' refers to a honey that is produced from nectar, at least about 50%, for example 75%, 85%, 95% or 98%, of which is derived from one or more Leptospermum species.
  • honey analogue containing MGO and other compounds or properties characteristic of honey may be used.
  • a honey fraction with the monosaccharide portion substantially removed may equally be used.
  • the phrase 'substantially removed' used above refers to a honey fraction containing less than at least about 50%, for example 75%, 85%, 95% or 98% of the saccharide concentration that would be found in the unfractionated honey.
  • the inventor's have unexpectedly found that comparatively small concentrations of honey or lactoferrin are required to achieve a yeast inhibitory effect when used in combination.
  • concentrations required are well below what might be expected from the individual components.
  • the composition may contain honey, honey analogue or honey fraction at a concentration of at least 1 % w/v in the composition.
  • the concentration may be at least 2%, for example, at least 3% , 4% , 5% , 6% , 7% , 8% , 9% , 10% , 12% , 15% , 18% , 20% w/v in the composition .
  • honey concentrations well above 20% w/ would likely be necessary to even begin to inhibit yeast growth. The order of magnitude difference conferred by the use of the combination of honey and lactoferrin is therefore highly unexpected.
  • the composition includes lactoferrin, being a compound or compounds that scavenge free transition metal ions, specifically iron in the case of lactoferrin.
  • Lactoferrin is known to inhibit yeast growth but in the inventor's experience, not to the extent demonstrated in from the combination with honey as described herein.
  • lactoferrin alone does not completely inhibit yeast growth.
  • the composition may include at least 0.1 mg/ml (0.1 % w/v) lactoferrin.
  • the lactoferrin concentration may be at least 0.2 mg/ml, 0.3 mg/ml, 0.4 mg/ml, 0.5 mg/ml, 0.6 mg/ml, 0.7 mg/ml, 0.8 mg/ml, 0.9 mg/ml, 1 mg/ml, 2 mg/ml, 3 mg/ml, 4 mg/ml, 5 mg/ml, 6 mg/ml, 7 mg/ml, 8 mg/ml, 9 mg/ml or 10 mg/ml (or % w/v).
  • lactoferrin may be used in a concentrated isolate form. Lactoferrin may also be used in an un-concentrated or dilute form such as from milk, colostrum, a milk concentrate or partial lactoferrin concentrate from a raw material source, or from a synthetic source (purified or non-purified form).
  • the honey analogue if used, may contain further characteristics of active honey. The inventors have found that an analogue with MGO and lactoferrin does not inhibit yeast growth to the same extent as a combination of active honey and lactoferrin. Modification of the honey analogue to include other characteristics of active honey may be completed to enhance the inhibitive effect.
  • Such characteristics to include may be selected from: use of a reduced pH, fortification with one or more phenolic compounds, fortification with bee defensins, use of a water activity of less than 0.7. It is the inventor's understanding however that hydrogen peroxide is not a contributing factor to the measured inhibitive effects. This has been confirmed in trials where the hydrogen peroxide content was knocked out via the use of catalase enzyme. The resulting inhibition was unchanged whether hydrogen peroxide was present or not.
  • the composition may contain one or more additional phenolic compounds.
  • the honey analogue if used may be fortified with one or more phenolic compounds.
  • the phenolic compounds may be selected from: phenolic acids, phenolic salts, phenolic esters, related polyphenoiic compounds, and combinations thereof .
  • the phenolic compounds may be methoxylated.
  • the applicant has analysed the phenolics prominent in manuka (Leptospermum spp.) and a large number of these phenolics are methoxylated at one or more points of their phenol or acid group.
  • Compounds such as gallic or benzoic acid may be present mainly in their methoxylated form such as methoxybenzoic acid, methoxygailic acid, methyl syringate, methoxyphenylactic acid or syringic acid.
  • Methoxylated phenolics may represent greater than for example 10% , 20% or 30% wt of the total phenolic compound content in the composition or contain at least 150 mg/kg of methoxylated phenolic compounds.
  • the phenolic compounds may be selected from: phenyllactic acid, methoxylated phenyllactic acid, methoxylated benzoic acids, syringic acid, methyl syringate, isomeric forms of methyl syringate, and combinations thereof.
  • Phenolic compounds may be present at a concentration in the composition of 5mg/kg to 10,000mg/kg.
  • the phenolic compounds used may be selected from: 2-methoxybenzoic acid and 4- methoxybenzoic acid.
  • honey fraction or honey analogue Fortification of the honey, honey fraction or honey analogue may be completed to achieve the above concentrations and/or to introduce one or more of the above types of phenolic compound.
  • the composition may include a carrier.
  • the carrier may be selected to suit the intended formulation or method of administration.
  • a wide variety of carriers or vehicles may be used.
  • the at least one carrier or vehicle has a melting point of about 37°C or greater.
  • the carrier may comprises from about 1 % to about 99.9% wt of the composition.
  • the composition may be in a form selected from: a liquid, a gel, a cream, an ointment, a wound dressing, a solid form tablet or capsule, and combinations thereof.
  • the carrier may be water. Water may be a useful carrier for liquid formulations or for encapsulated formulations.
  • the carrier may be a powder or granular substance into which the composition is incorporated, for example for administration via a tablet or capsule.
  • the above carriers may be selected based on whether the composition is to be formulated for internal use or external use.
  • a method of inhibiting yeast growth by administrating a composition substantially as described above to a subject in need thereof.
  • a composition substantially as described above in the manufacture of a medicament to inhibit yeast growth.
  • the composition may have a variety of treatment applications to inhibit yeast growth and thereby allow other treatment measures to take effect.
  • the composition may be applied to a wound, skin or mucus lining to inhibit yeast growth, while the patient is co-administered a traditional anti-fungal remedy. This dual approach avoids the region becoming further infected, slows spread of the infection and allows time for the traditional antifungal remedy to take effect.
  • composition may be administered topically to a subject.
  • Topical treatments using honey based dressings and formulations are well known in the art and the combination described herein provides an added and potentially more potent method of treatment.
  • the composition may be an aqueous based medicament such as a cream or gel that is rubbed onto the skin or mucus lining(s) of the subject to directly treat an infection or instead, to prevent secondary infections related to fungi or yeast.
  • the subject may be a human.
  • the subject may be a non-human animal.
  • humans and animals can equally be treated using the yeast inhibitory composition as the physiology of a yeast based infection may be similar between humans and at least other mammals.
  • animals to which the composition may be administered include horses, livestock including cattle, sheep and deer and companion animals such as cats and dogs.
  • a yeast inhibitive wound dressing including a composition substantially as described above. .
  • a yeast inhibitive aqueous based medicament including a composition substantially as described above.
  • wound dressings and aqueous based medicaments incorporating honey are well known and researched. Examples include those described in at least
  • the dressing or aqueous based medicament may include at least one gelling agent.
  • gelling agents are advantageous for use with honey for wound
  • the gelling agents reduce the tackiness of the honey, yet provide a more cohesive structure such as a sheet structure or viscous gel that is easier to apply to a wound, skin region or mucosal lining.
  • Gelling agents also have the advantage that they may be absorbent and work to move exudate away from a wound environment. This consequently avoids dilution of the honey and lactoferrin at the site.
  • the gelling agent may be selected from: an absorbent synthetic polymer, an absorbent natural based polymer, and combinations thereof.
  • the absorbent synthetic polymer may be selected from: any cross-linked sodium polyacrylate, polyacrylamide copolymer, ethylene maleic anhydride copolymer, carboxymethyl cellulose, polyvinyl alcohol copolymer, isobutylene-maleic anhydride copolymer, cross-linked polyethylene oxide, starch grafted copolymer or polyacrylonitrile, gauze, and combinations thereof.
  • the absorbent natural based polymer may be selected from: alginate, agar, natural based gums, and combinations thereof.
  • the alginate may be selected from: calcium alginate, sodium alginate, and combinations thereof.
  • the gelling agents may be present as a powder, granule or fibre.
  • compositions may be added to the described composition and/or co-administered.
  • One example envisaged is the co-administration of clotrimazole anti-fungal agent with the composition of the above embodiments. In this way, irrespective of any potential synergies, the user need only administer a single composition rather than multiple compositions.
  • the composition may be irradiated with a sterilisation effective dose of radiation.
  • the dose may be for example, 5kGy, 10kGy, 15kGy, 20kGy, 25kGy or 30kGy, the amount dependent on the end application and what is required in order to sufficiently sterilise the composition and meet market regulatory approvals.
  • compositions, methods and uses are now described with reference to examples illustrating embodiments of the composition.
  • a manuka honey was mixed with lactoferrin at varying concentrations and the degree of Candida albicans growth was measured and compared to each of the individual components alone.
  • honey was diluted with distilled water to honey concentrations Of 12.5, 11 .25, 10, 8.75, 7.5 and 0 %(w/v).
  • Microbial growth for each of the samples was then measured every 2hrs continuously for up to 24hrs, determined by measuring the optical density of the mixture.
  • honey and lactoferrin both inhibit microbial growth compared to not having honey or lactoferrin present at all.
  • the degree of inhibition was relatively low.
  • Candida albicans repeat trials were completed where the growth of Candida albicans cultures in broth was measured when subjected to a 10% w/v manuka honey with 1 mg/ml catalase and lactoferrin treatments ranging from 2.5-10 mg/ml.
  • the assay temperature was 28°C as used previously.
  • the assay was a broth microtitre plate set-up. Growth was measured by absorbance at 650nm. Catalase was added to remove the peroxide effect noted above.
  • Figure 6 confirms the combination inhibition (almost 100% inhibition) and minimal inhibition with honey alone or lactoferrin alone.
  • Figure 6 illustrates the results using a 10% w/v honey dilution. Similar repeats were also completed for 5% w/v and 15% w/v honey dilutions and these gave the same resutls as that shown in Figure 6 for a 10% w/v dilution.
  • honey analogue was compared to various controls and honey and lactoferrin combinations.
  • the growth of Candida albicans cultures in broth were subject to 10% w/v manuka honey with 1 mg/ml catalase treatment, artificial honey (honey analogue) and methylglyoxal (MGO) treatments relative to the honey treatment, and lactoferrin treatments ranging from 7.5-10 mg/ml.
  • Catalase was added to remove the peroxide effect noted above.
  • honey analogue used was a sugar syrup containing MGO equivalent to that found in the manuka honey used in the trial.
  • the honey analogue did not achieve the same degree of inhibition as the honey and lactoferrin combination tested even when used with comparative concentrations of lactoferrin. This illustrates that the synergism is in part due to aspects such as peroxide activity, osmolarity and MGO content but also requires another characteristic seen in the combination of manuka honey and lactoferrin.
  • Characteristics that may be attributable to the full inhibition effects observed for active honey beyond just MGO and lactoferrin alone include: the pH of honey, the presence of hydrogen peroxide, the presence of one or more phenolic compounds, the presence of bee defensins or a water activity of 0.7,
  • compositions described in earlier examples are administered to treat a topical wound or yeast infection of a mucus lining.
  • a composition may be manufactured by preparing any one of the mixtures as follows: Mixture 1 : manuka honey and lactoferrin Mixture 2: jellybush honey and lactoferrin
  • Mixture 3 a honey analogue including glucose, fructose, peroxidase enzyme, DHA and MGO, tannins extracted from manuka honey along with lactoferrin
  • Mixture 4 a non-peroxide activity containing fraction of honey with 95% of all monosaccharides removed with lactoferrin
  • the mixtures are applied to a wound on a human or an animal e.g. a horse.
  • the mixtures may be formulated as per existing wound dressings e.g. those described in US 7,714,183, US 6,956,144, US 11/106,473, US 12/091 ,897, US 12/301 ,931.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Insects & Arthropods (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Zoology (AREA)
  • Animal Husbandry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Dermatology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

L'invention concerne des compositions qui présentent un effet d'inhibition de la croissance de la levure qui, de façon inattendue, est supérieur à celui des composants individuels seuls. Les compositions comprennent un mélange de miel, d'un analogue de miel ou d'une fraction de miel conjointement avec la protéine lactoferrine. La combinaison présente un effet synergique dans l'inhibition de la croissance de la levure.
PCT/NZ2011/000172 2010-08-30 2011-08-29 Composition antifongique Ceased WO2012030231A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP11822182.9A EP2611453B1 (fr) 2010-08-30 2011-08-29 Composition antifongique
CA2809535A CA2809535C (fr) 2010-08-30 2011-08-29 Composition antifongique
AU2011296641A AU2011296641B2 (en) 2010-08-30 2011-08-29 Antifungal composition
US13/819,629 US20130273020A1 (en) 2010-08-30 2011-08-29 Antifungal composition

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
NZ587642 2010-08-30
NZ58764210 2010-08-30

Publications (1)

Publication Number Publication Date
WO2012030231A1 true WO2012030231A1 (fr) 2012-03-08

Family

ID=45773103

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/NZ2011/000172 Ceased WO2012030231A1 (fr) 2010-08-30 2011-08-29 Composition antifongique

Country Status (5)

Country Link
US (1) US20130273020A1 (fr)
EP (1) EP2611453B1 (fr)
AU (1) AU2011296641B2 (fr)
CA (1) CA2809535C (fr)
WO (1) WO2012030231A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016083798A1 (fr) * 2014-11-24 2016-06-02 Matoke Holdings Limited Prévention et traitement d'infections microbiennes
WO2018065608A1 (fr) * 2016-10-06 2018-04-12 Matoke Holdings Limited Compositions antimicrobiennes
US11185080B2 (en) 2014-04-30 2021-11-30 Matoke Holdings Limited Antimicrobial compositions
US11730168B2 (en) 2017-10-16 2023-08-22 Matoke Holdings Limited Antimicrobial superabsorbent compositions

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107708752A (zh) * 2015-02-03 2018-02-16 玛托克控股有限公司 抗微生物纤维和组合物
CL2017000766A1 (es) 2017-03-30 2017-12-01 Janette Arroyo Perez Patricia Bioproducto a base de nanopartículas de selenio en matriz miel, para el tratamiento de heridas complejas e infecciones dermatológicas

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2220708C1 (ru) * 2002-12-16 2004-01-10 Открытое акционерное общество "Косметическое объединение "Свобода" Крем омолаживающий "молоко и мед"
WO2007137881A1 (fr) * 2006-06-01 2007-12-06 Sano Medical Bvba Produit de soins pour blessures
WO2008049578A2 (fr) * 2006-10-27 2008-05-02 Cnci Bvba Procédé de stérilisation de miel cru non réchauffé, préparation de soins de plaies à base de miel, et biscuit à base de miel
WO2010082846A1 (fr) * 2008-12-24 2010-07-22 Comvita New Zealand Limited Formulations médicales et nutritionnelles

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7125963B2 (en) * 2004-03-03 2006-10-24 En N Tech Inc Treatments for contaminant reduction in lactoferrin preparations and lactoferrin containing compositions
NZ533368A (en) * 2004-06-08 2008-06-30 Univ Waikato Isolation process
ES2526640T3 (es) * 2005-11-18 2015-01-14 Glanbia Nutritionals (Ireland) Limited Composiciones para romper e inhibir la reconstitución de la biopelícula de heridas
US8568790B2 (en) * 2006-05-31 2013-10-29 Medihoney Pty Ltd. Medicinal compositions containing honey
GB0616580D0 (en) * 2006-08-21 2006-09-27 Novathera Ltd Composite material

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2220708C1 (ru) * 2002-12-16 2004-01-10 Открытое акционерное общество "Косметическое объединение "Свобода" Крем омолаживающий "молоко и мед"
WO2007137881A1 (fr) * 2006-06-01 2007-12-06 Sano Medical Bvba Produit de soins pour blessures
WO2008049578A2 (fr) * 2006-10-27 2008-05-02 Cnci Bvba Procédé de stérilisation de miel cru non réchauffé, préparation de soins de plaies à base de miel, et biscuit à base de miel
WO2010082846A1 (fr) * 2008-12-24 2010-07-22 Comvita New Zealand Limited Formulations médicales et nutritionnelles

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
AL-JABRI A.A. ET AL.: "Honey, milk and antibiotics", AFRICAN JOURNAL OF BIOTECHNOLOGY, vol. 4, no. 13, December 2005 (2005-12-01), pages 1580 - 1587, XP055077182 *
See also references of EP2611453A4 *

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11185080B2 (en) 2014-04-30 2021-11-30 Matoke Holdings Limited Antimicrobial compositions
US11311017B2 (en) 2014-04-30 2022-04-26 Matoke Holdings Limited Antimicrobial compositions
WO2016083798A1 (fr) * 2014-11-24 2016-06-02 Matoke Holdings Limited Prévention et traitement d'infections microbiennes
GB2547402A (en) * 2014-11-24 2017-08-16 Matoke Holdings Ltd Prevention and treatment of microbial infections
GB2547402B (en) * 2014-11-24 2018-03-28 Matoke Holdings Ltd Prevention and treatment of microbial infections
EP3603654A1 (fr) * 2014-11-24 2020-02-05 Matoke Holdings Limited Prévention et traitement d'infections microbiennes
WO2018065608A1 (fr) * 2016-10-06 2018-04-12 Matoke Holdings Limited Compositions antimicrobiennes
JP2019533661A (ja) * 2016-10-06 2019-11-21 マトケ・ホールディングス・リミテッド 抗微生物組成物
US11730168B2 (en) 2017-10-16 2023-08-22 Matoke Holdings Limited Antimicrobial superabsorbent compositions
US12225905B2 (en) 2017-10-16 2025-02-18 Matoke Holdings Limited Antimicrobial superabsorbent compositions

Also Published As

Publication number Publication date
CA2809535A1 (fr) 2012-03-08
EP2611453A1 (fr) 2013-07-10
EP2611453B1 (fr) 2021-08-18
US20130273020A1 (en) 2013-10-17
AU2011296641A1 (en) 2014-02-13
CA2809535C (fr) 2017-04-04
AU2011296641B2 (en) 2015-07-02
EP2611453A4 (fr) 2014-02-26

Similar Documents

Publication Publication Date Title
EP2155222B1 (fr) Extrait de trigonella foenum-graecum
EP2775838B1 (fr) Composition antimicrobienne aqueuse contenant des acides de résines de conifères
US20190008905A1 (en) Compositions for management of wounds, skin diseases, dehydration, chronic diseases, and respiratory diseases
CA2809535C (fr) Composition antifongique
US20180064775A1 (en) Anti-pathogenic compositions
Subrahmanyam Addition of antioxidants and polyethylene glycol 4000 enhances the healing property of honey in burns
AU2020203300A1 (en) Anti-inflammatory compositions, methods and uses thereof
US11109607B2 (en) Oil-based compositions for enhancing oral health and general wellness in humans
Sekar et al. Antimicrobial properties of honey
WO2008104076A1 (fr) Préparation antimicrobienne à base d'argent électro-colloïdal et de racine d'échinacée
AU2014311968A1 (en) Anti-inflammatory compositions, methods and uses thereof
HK1045813A1 (en) Non-solid composition for local application comprising glycerol and alchemilla vulgaris extract
Bano Unlocking the therapeutic potential of honeybee products: a comprehensive review
CN104055720A (zh) 止痒护肤水
AU2006203630B2 (en) Intramammary formulations
US20080050456A1 (en) Intramammary formulations
Lata et al. Honey as Wound Dressing and Healing Agent
Magdhum A Sweet Science of Healing: Unravelling the Remarkable Molecular Mechanisms behind Honey's Wound-Healing Properties
Waykar et al. Indian Journal of Pharmaceutical and Biological Research (IJPBR)
WO2011046454A1 (fr) Traitement du molluscum contagiosum avec du miel
Yelmame et al. Exploring the healthcare benefits of honeybee products: A comprehensive review
NZ534973A (en) Intramammary formulations
WO2016081478A1 (fr) Compositions à base d'huile pour améliorer la santé buccale et le bien-être général d'êtres humains

Legal Events

Date Code Title Description
DPE2 Request for preliminary examination filed before expiration of 19th month from priority date (pct application filed from 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 11822182

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2809535

Country of ref document: CA

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 2011822182

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 13819629

Country of ref document: US

ENP Entry into the national phase

Ref document number: 2011296641

Country of ref document: AU

Date of ref document: 20110829

Kind code of ref document: A